Diffuse intrinsic pontine glioma (DIPG) is an incurable paediatric malignancy. Identifying the molecular drivers of DIPG progression is of the utmost importance. Long non-coding RNAs (lncRNAs) represent a large family of disease- and tissue-specific transcripts, whose functions have not yet been elucidated in DIPG. Herein, we studied the oncogenic role of the development-associated lncRNA in DIPG. Bioinformatic analyses of clinical datasets were used to measure the expression of lncRNA in paediatric high-grade gliomas (pedHGGs). The expression and sub-cellular location of lncRNA were validated in DIPG cell lines. Locked nucleic acid antisense oligonucleotides were designed to test the function of in DIPG cells. We found that expression was higher in DIPG vs. normal brain tissue and other pedHGGs. knockdown resulted in decreased cell proliferation and survival in DIPG cells. Mechanistically, buffers microRNAs, resulting in the up-regulation of oncogenic target (e.g., and ). is the first functionally characterized lncRNA in DIPG and a promising therapeutic candidate for treating this incurable cancer.
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http://dx.doi.org/10.3390/ijms22179165 | DOI Listing |
Eur J Cancer
January 2025
ACCELERATE, Europe; Gustave Roussy Cancer Centre, Paris, France.
Fewer than 10 % of children with diffuse midline glioma (DMG) survive 2 years from diagnosis. Radiation therapy remains the cornerstone of treatment and there are no medicinal products with regulatory approval. Although the biology of DMG is better characterized, this has not yet translated into effective treatments.
View Article and Find Full Text PDFCell Rep Med
January 2025
Department of Immunology and Regenerative Biology, Weizmann Institute of Science, Rehovot, Israel. Electronic address:
The analysis of cell-free tumor DNA (ctDNA) and proteins in the blood of patients with cancer potentiates a new generation of non-invasive diagnostic approaches. However, confident detection of tumor-originating markers is challenging, especially in the context of brain tumors, where these analytes in plasma are extremely scarce. Here, we apply a sensitive single-molecule technology to profile multiple histone modifications on individual nucleosomes from the plasma of patients with diffuse midline glioma (DMG).
View Article and Find Full Text PDFNat Med
January 2025
Seattle Children's Therapeutics, Seattle, WA, USA.
Diffuse intrinsic pontine glioma (DIPG) is a fatal central nervous system (CNS) tumor that confers a median survival of 11 months. As B7-H3 is expressed on pediatric CNS tumors, we conducted BrainChild-03, a single-center, dose-escalation phase 1 clinical trial of repetitive intracerebroventricular (ICV) dosing of B7-H3-targeting chimeric antigen receptor T cells (B7-H3 CAR T cells) for children with recurrent or refractory CNS tumors and DIPG. Here we report results from Arm C, restricted to patients with DIPG.
View Article and Find Full Text PDFFront Oncol
December 2024
Department of Pediatric Hematology-Oncology and Blood & Marrow Transplant, Cleveland Clinic, Cleveland, OH, United States.
Pediatric diffuse midline glioma (DMG), including diffuse intrinsic pontine glioma (DIPG), are aggressive brainstem tumors with a dire prognosis, traditionally diagnosed based on MRI characteristics. The recognition that molecular characteristics may determine prognosis and response to therapy has led to a reevaluation of biopsy necessity. This comprehensive review addresses the evolving role of brainstem biopsies in diagnosing and managing these tumors - both within the context of a clinical trial and in routine clinical care.
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